Associations of Serum Neurofilament Light Chain with Outcomes in Children with Autoimmune Encephalitis (P4-5.009)

Abstract

<h3>Objective:</h3> To examine associations between serum neurofilament light chain (sNfL) levels at disease onset with markers of clinical severity in children with autoimmune encephalitis (AE). <h3>Background:</h3> Despite significant advances in the diagnosis and treatment of AE, little is known about markers of disease severity and their associations with outcomes. sNfL, a marker of axonal destruction, may fill this gap. <h3>Design/Methods:</h3> This is a longitudinal prospective case-control study of children presenting to a single tertiary center with AE (n=48) vs. an age-matched healthy control population (HC) (n=88). Clinical data and modified Rankin Scale (mRS) scores were collected using a standard CRF at baseline and at follow-up, up to one year. sNfL levels in stored samples were measured by Single Molecule Array Immunoassay (SIMOA). Volumetric analyses of key anatomic structures of brain MRIs were performed using FreeSurfer. Diffusion weighted MRI was assessed for restricted diffusion. Following standard diagnostic criteria, children were classified into those with no biological marker (antibody or genetic) and those with. We further dichotomized children into high vs. low sNFL levels. Descriptive statistics, group differences, and correlational analyses were performed using JASP version 0.16.3. <h3>Results:</h3> Baseline sNfL levels were significantly higher in patients with AE (no Ab), AE (MOG), and ANEC vs. HCs (log₂ sNfL=4.3 AE(no Ab), 2.9 AE(NMDA), 5.6 AE(MOG), 6.3(ANEC), 2.4(HC), <i>p</i>&lt;0.001). AE patients in the high sNfL group were more likely to be admitted to the ICU (<i>p</i>=0.02) and had significantly higher mRS scores at nadir (<i>p</i>=0.04), compared to patients in the low sNfL group. However, there was no significant difference in mRS scores at follow-up between groups. Baseline sNfL correlated significantly with baseline restricted diffusion (r_s(43)=0.45, <i>p</i>=0.002) and thalamic volumes (r_s(31)=0.45, <i>p</i>=0.009). <h3>Conclusions:</h3> Baseline sNfL levels may serve as a marker of disease severity in patients with AE. Future studies are needed to evaluate their associations with long-term outcomes. <b>Disclosure:</b> Ms. Da Silva has nothing to disclose. Ms. Yea has nothing to disclose. Dr. AlYanbuaawy has nothing to disclose. Dr. Matt has nothing to disclose. Dr. Longoni has nothing to disclose. Helen Branson has nothing to disclose. Logi Vidarsson has nothing to disclose. An immediate family member of Dr. Ertl-Wagner has received personal compensation for serving as an employee of Siemens Healthineers. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for PRIME. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Yeh has received research support from Biogen. The institution of Dr. Yeh has received research support from Stem Cell Network. The institution of Dr. Yeh has received research support from CIHR. The institution of Dr. Yeh has received research support from Ontario Institute for Regenerative Medicine. The institution of Dr. Yeh has received research support from National MS Society. The institution of Dr. Yeh has received research support from NIH. The institution of Dr. Yeh has received research support from SickKids Foundation. The institution of Dr. Yeh has received research support from CMSC. The institution of Dr. Yeh has received research support from MSSC.